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Gene Therapy Needs Machines

News came recently of an apparent cure, via gene therapy, of sickle-cell disease in a young patient (whose condition was refractory to hydroxyurea and the other standards of care). Blood-cell diseases are naturally one of the main proving grounds for things like this, since their stem cell populations are in easily localizable tissues and the techniques for doing a hard reset/retransplantation on them are (in some cases) well worked out.

This is an important result, but all such approaches face a possible disconnect as they move forward. As it stands, such gene therapy is a rather expensive and labor-intensive process. Patients are carefully identified and handled one at a time, and there are a limited number of medical centers in the entire world that can operate at this level. The problem is, none of them are particularly close to the great majority of people who actually have sickle cell disease. You can get up to nearly 60% of the worldwide population of sickle cell patients just by counting some regions of India, all of Nigeria, and (even tougher) the Democratic Republic of the Congo. There are sickle-cell populations in many countries because of migration, but most of the births are occurring in sub-Saharan Africa.

Is there any hope that gene therapy and cell replacement could get to the point that you could carry it out at a useful rate in some of the places where it would be needed the most? That’s going to to hard, but this article at Technology Review by Antonio Regalado shows some progress:

In October, (Jennifer) Adair demonstrated a new technology she thinks could democratize access to gene therapy. Tweaking a cell-processing device sold by German instrument maker Miltenyi, she mostly automated the process of preparing blood cells with a gene therapy for HIV that her center is also testing. Cells dripped in one end came out the other 30 hours later with little oversight needed. She even added wheels. Adair calls the mobile lab “gene therapy in a box.”

Adair thinks a key job for the mobile gene-therapy lab is to extend experimental studies to the developing world, including Africa, where most HIV cases are. “We wanted to show that we could make the trial mobile, because we are kidding ourselves that treating someone in Seattle is going to have the same risks and outcomes as in South Africa,” she says.

The many companies that are working on such therapies seem to be paying attention to this sort of work, because it’s not only a possible path to getting clinical trials run (and eventually patients treated) in the regions where most such patients are to be found. Companies are going to be selling such things first to people in the wealthier developed countries, but that’s only the beginning of the story (as it has been with antiretroviral drugs). Everyone in the field needs better and faster to turn these sorts of cell therapies around, just on the research end. The amount of work needed now is a significant bottleneck not only for such therapies that exist (or are close to existing), but for the development of better ones. I spoke about automation in drug discovery last year at Manchester, and about the good sides and bad sides of it. But this sort of thing is an easy call: a lot of intelligent, highly trained people could be doing a lot more with their time if machines were able to pick up more of the load.

12 comments on “Gene Therapy Needs Machines”

  1. Ben says:

    Would really like to see a blog post about the talk you gave in Manchester Derek.

    1. Grant says:

      Second this!

    2. Interest in Automation says:

      Yes! It would be very interesting to read what you have to say about this topic!

    3. Derek Lowe says:

      Sounds good – I’ve written a bit about the topic here, but I think a longer post just on that subject would be worthwhile. Look for one soon!

  2. pete says:

    This is an interesting approach.

    That said, I can imagine it might also fire up the imagination of some unintended users: “Cool — this gene transduction lab-in-a-box should fit nicely into the baggage hold of the cycling team bus”.

  3. Anon says:

    Just need to engineer sub-saharan mosquitos to deliver this gene therapy (instead of malaria) and we’re sorted. Simples. But the FDA block that kind of thing. Sad!

  4. Barry says:

    more attractive to my eye for gene therapy are the various hemophilias. No need to delete anything. Just add a gene for the broken clotting factor under the right promoter, with an export tag for the plasma compartment. Don’t have to care much what tissue is expressing the added clotting factor–as long as it’s not making too much. So transduction can be done in-situ.

    1. skeptic says:

      Too much would definitely be a problem, though. The possibility of excessive bleeding is bad, but compared to a stroke or heart attack, maybe not *that* bad.

      I suspect that the machinery for regulating such a promoter wouldn’t be present in most cells.

      1. Barry says:

        may need to put in a failsafe (promoter dependent on an exogenous drug?). But expression of genes transduced in adults historically has been quite low, I think (valuable in a hemophiliac who makes zero, albeit unlikely to achieve “normal” levels)

  5. TroyBoy says:

    I looked into the possibility of doing a clinical trial for a disease that primarily affects African countries, but is also seen in Western countries. I was quickly admonished (by a Western academic physician working there) not to pursue that route because (1) they don’t have the infrastructure to do a clinical trial and (2) they have no interest in doing clinical trials in a patient population that would not have access to the medication later, if approved. She warned me that the IRB (or ethics committee) would take a dim view with respect to a clinical trial, if–after (a theoretical) approval–the prices were too high, that the patients wouldn’t benefit. Even relatively mundane observational studies were difficult to get through the IRB if direct benefits to the local population were not obvious.

    I don’t know what the underlying costs might be in gene therapy, but companies will need to consider it before trying to get a clinical trial approved by a foreign IRB.

  6. M says:

    Derek, would you consider posting your slides from that talk here? It would be great to see them! Probably would lead to good discussion here…

  7. jbosch says:

    Or put your slides up on Slideshare perhaps?

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